Termites, and related insect pests, constitute a significant economic threat in a modern society. While conventional insecticides, typically chlorinated hydrocarbons such as chlordane, DDT, aldrin, dieldrin and BHC can be effectively utilized to eradicate these pests, such insecticides pollute water, contaminate soil, and are toxic to many life forms. Chlordane is the only chlorinated hydrocarbon that has not yet been banned, principally because a suitable substitute having its effectiveness has yet to be found. However, it still accumulates in the environment and causes food chain elimination since, for instance, an earthworm may be resistant to its poison, but the bird which consumes many such earthworms may die or be rendered infertile. An environmentally inactive chemical is thus needed to obviate food chain problems. While the chlorinated hydrocarbon insecticides are economical to product, the cost of the resulting environmental cleanup makes their use expensive in the long run. Thus, there exists a substantial need for new environmentally safe and effective pesticides.
One of the most distinctive areas of biochemical and physiological difference between insects and vertebrates is the steroid metabolism of insects. See, for instance,
Svoboda and Thompson, "Comparative sterol metabolism in insects", p. 1-16; and Morisaki et al., "Sterol metabolism of the silkworm Bombyx mori", pp. 17-26; both in Metabolic aspects of lipid Nutrition in Insects, pp. 1-16, edited by Mittlerand Dadd, Westview Press, 1983;
Kircher, "Sterols and insects," in Cholesterol Systems in Insects and Animals, edited by Dupont pp. 1-50, CRC Press, 1982;
and Svoboda et. al., "Insect steroid metabolism," Lipids 13: 742-753 (1978).
Analogous to the use of pro-drugs in chemotherapy, pro-insecticides can be designed such that an insect enzyme converts a less toxic precursor into an inactivator of a specific protein. If the same protein catalytic site is involved in both unmasking and irreversible binding of a reactive species, then the pro-insecticide is considered to be a suicide substrate. See, for instance, Walsh, "Suicide substrates: mechanism-based enzyme inactivators", Tetrahedron 38: 871-909 (1982).
Fluoroactetate undergoes a "lethal synthesis" to .alpha.-fluorocitrate, which may either inhibit aconitase or a membrane-associated citrate transport protein. Insecticidal and other biocidal uses of fluoroacetate (or its metabolic precursors) previously received considerable attention many years ago, but most uses have been abandoned due to the inherently high toxicity of these compounds to vertebrates. (see, for instance, Pattison, Toxic Aliphatic Fluorine Compounds, Elsevier Press, 1959).
Utilizing the phytosterol dealkylation pathway unique to phytophagous insects, the latent poison fluoroacetate can be released in vivo. Additionally, it would be advantageous to release the fluoroacetate from a "masked" poison which could not be activated by vertebrates.
Most plant-eating insects degrade sitosterol (I) via fucosterol (II), fucosterol epoxide (III), and desmosterol (IV) to cholesterol (V). See, Scheme I below. Stigmasterol (VI) as degraded analogously via the cholestatrienol (VII). See, Scheme I, below: ##STR1## those in the nest continue to multiply and thus the infestation remains. A delayed onset of toxic effects would allow for the insects to return poisoned food to the entire colony and thereby poison all the occupants. Thus in addition to high toxicity, an effective termite and insect pest poison must have a delayed onset of activity and be easily transferably to other members of a given colony.
Furthermore, an effective pesticide must possess the more subtle characteristic of not only being a "non-repellent", but should most advantageously be an "attractant." This simply means that a feeding termite would not prefer another food source over the poisoned source and ideally would even prefer the poisoned source over a regular food supply. Additional characteristics of an ideal pesticide would be nonleachability, i.e. poor solubility in water, and stability, i.e., but readily degraded in the soil.